This invention relates to a field effect transistor transducer adapted for detection and measurement of various chemical properties such as ion activity.
There has been a continuing search for improved methods of in vivo detection, measurement and monitoring of chemical properties. ("Chemical properties", as used herein, shall be understood to include ion activity and concentration, presence and concentration of enzymes, substrates, antibodies, antigens, hormones and reducible gases and the presence, concentration and activity of any of a variety of chemical and biochemical substances.) For example, in patients with arrhythmias, cardiogenic shock, and myocardial infarctions, various ion concentrations in the body of the patient may shift dramatically in the course of treatment of the patient and measurement and monitoring of such shifts can provide an important indication as to the well being of the patient. Change of ion concentration in the body of a patient is also common during open heart or major vascular surgery, during pharmacological therapy, the administration of fluids and electrolytes to the body, and during numerous other types of medical procedures and treatments. Such measurement and monitoring may be required on a fairly continuous basis or only at infrequent intervals, but in either case it is desirable that the measurement and monitoring be conducted as accurately as possible and with the least amount of physical discomfort to the patient.
There are also a variety of situations, both in vivo and in vitro, where it would be desirable to efficiently and accurately monitor or measure the concentration of biochemicals such as the concentration of the constituents of enzymatic systems including serum enzymes, glucose, lactic acid, pyruvic acid, creatinine, urea, etc., and the constituents of immunochemical systems. In all these situations, there is a need for miniaturizing the measuring apparatus and for improving the speed and reducing the cost of performing the measurements.
Detection, measurement and monitoring of chemical properties of a substance generally involves measurement of potential difference between two electrodes, with such potential difference being dependent upon the chemical activity being measured. Apparatus for performing such measurement, at least of ion activity, has typically included the use of glass electrodes having a hydrated glass layer. Such electrodes, however, are fairly limited as to the type of chemical properties which can be measured with only cation sensitive glass electrodes known to be presently available. See G. J. Moody and J. D. R. Thomas, Selective Ion Sensitive Electrodes, Merrow Publishing Co. Ltd., Watford, England, 1971.
Other prior art apparatus for measuring ion activity include solid state, homogeneous and heterogeneous electrodes and liquid ion exchanger membrane electrodes. See Moody and Thomas, supra. This apparatus is generally quite costly to construct, bulky and, as with glass electrodes, limited as to the types of electrochemical properties which it can measure.
A fairly recent development in apparatus for measuring ion activities is disclosed in "Development, Operation, and Application of the Ion-Sensitive Field-Effect Transistor as a Tool for Electrophysiology" by Piet Bergveld, IEEE Transactions of Biomedical Engineering, September, 1972, pages 342-351. Bergveld suggested the use of a metal oxide semiconductor Field-effect transistor (MOSFET) modified by removal of the gate metal, for measuring hydrogen and sodium ion activities in an aqueous solution. In particular, it was suggested that a MOSFET be constructed without the gate metal so that when the transistor were placed in an aqueous solution, the oxide (silicon dioxide) insulation layer would become hydrated and then, with the presence of impurities in the hydrated layer, ion selective. After hydration of the insulation layer of the MOSFET, the device, it was suggested, could be used for ion activity measurement by immersing the device in the solution in question and then recording conductivity changes of the device.
One problem with the device suggested by Bergveld is that immersion of the device in an aqueous solution results in continuation of the hydration process of the oxide insulation layer. Such a continuation of the hydration process would, of course, affect the accuracy of the ion activity measurements and, after a fairly short period of time, would result in shorting out the device, 1.e., conduction through the device from the source electrode to the drain electrode would ultimately occur not through the conducting channel, but rather through the hydrated insulation layer.
An arrangement similar to that disclosed by Bergveld was described in "An Integrated Field-Effect Electrode for Bipotential Recording" by T. Matsuo and K. D. Wise, IEEE Transactions on Biomedical Engineering, November, 1974, pages 485-487. The device there disclosed, however, was designed for measuring biopotential differences and not for selectively measuring various chemical properties.
Another device of interest, designed to measure the concentration of various reducible gases, is disclosed in U.S. Pat. No. 3,719,564. This device comprises a solid-state electrochemical cell having a pair of electrodes and a rare earth fluoride electrolyte sandwiched therebetween. The concentration of certain reducible gases is measured by exposing the cell to a medium containing such gas and recording the cell current which, it has been determined, is a function of the concentration of the gas.